Why do some recover quickly and others don’t?


Why some people recover from Lyme disease while others experience months, years, or even decades of chronic symptoms has long puzzled doctors. New research offers some clues about an immune system marker in the blood that is elevated among people with persistent symptoms of Lyme disease, even after receiving antibiotics.

In it new studypublished May 9 in the Centers for Disease Control and Prevention journal Emerging Infectious Diseases, researchers found that an immune system marker in the blood called interferon-alpha was elevated among people who had been treated for the disease. Lyme but had persistent symptoms.

Interferon-alpha is one of the few key signaling proteins that the body makes to tell immune cells to fight bacteria or viruses. If blood levels are too high, the immune system can overreact, causing pain, swelling, and fatigue—symptoms often seen in Lyme disease.

In patients with high levels of interferon-alpha, the immune response to Lyme bacteria can cause chronic inflammation, even after the infection clears up, said Klemen Strle, a research assistant professor of molecular biology and microbiology at Tufts University and article author. new study

“We think this is a possible driver of persistent symptoms,” Strle said. And since several drugs are already approved to reduce interferon alpha, she suggested that the research could mean a possible treatment option for persistent Lyme symptoms.

The study was small, including 79 people diagnosed with Lyme disease, and found only an association between higher levels of interferon-alpha and persistent Lyme disease symptoms, not that the immune marker itself was causing the symptoms. lasting symptoms. A larger clinical trial would be needed to confirm the connection.

Adult male and female blacklegged ticks, Ixodes scapularis, on a sesame seed bun to show their relative size.Centers for Disease Control and Prevention

Between 30,000 and 500,000 people develop Lyme disease from a tick bite each year, according to the C.DC. For most, the infection is mild and easily treated with antibiotics. About 10% experience symptoms such as fatigue and brain fog along with muscle, joint, and nerve pain that persists even after treatment.

The new findings represent a significant shift in understanding why some people infected with Lyme suffer from chronic symptoms. Previously, some researchers believed that a specific strain of the spiral-shaped Borrelia burgdorferi bacterium that causes Lyme could be the cause. Others wondered if undetectable low levels of infection remained in the body after treatment. The new research suggests that the way the body reacts to the bacteria, not the insect itself, could lead to long-lasting symptoms.

It’s still not clear why some people have elevated interferon alpha, but Strle said he’s looking into a possible genetic cause.

Although the interferon-alpha research is still in its early stages, Dr. Roberta DeBiasi, chief of the division of pediatric diseases at Children’s National Hospital in Washington, DC, called it «very well designed and interesting.»

“It provides a potential therapeutic target that could be studied in clinical trials to treat these patients,” he said.

For people facing ongoing Lyme symptomsany biological explanation for the condition called post-youlyme treatment ddiscomfort yessyndromeor PTLDS, it’s a step up.

Years of Lyme symptoms

Rebecca Greenberg isn’t entirely sure when she first contracted Lyme disease, but she has her suspicions. Greenberg, now 26, vividly remembers her mother removing a small, firm tick from the back of her neck with tweezers after they had been playing on a playground near Albany, New York, when she was 9 years old. She may have had multiple tick bites during her time in the Adirondacks, but she didn’t worry about them until she started feeling sick at age 15.

“I was so tired that I kept telling my mom that I couldn’t get up for school anymore,” said Greenberg, who grew up in upstate New York but now lives in south Florida. “My muscles ached, my joints ached, and I would get these migraines.”

Rebecca Greenberg.
Rebecca Greenberg.Courtesy of Rebecca Greenberg

Doctors told Greenberg that her symptoms were likely hormonal, and when Greenberg arrived at the emergency room unable to move the left side of her body, they prescribed anti-anxiety medication and suggested she see a neurologist. Those doctors weren’t much help either, Greenberg said. His symptoms eventually became so severe that he stopped attending school and required a wheelchair.

It wasn’t until 2011, after Greenberg’s mother posted on Facebook about her daughter’s mysterious illness, that a pediatrician friend suggested Lyme disease. Antibody tests soon showed that Greenberg had been infected with Lyme and two other bacterial infections, babesiosis and bartonella.

Even now, she is still dealing with fatigue and nerve pain. The most debilitating symptoms of her Lyme disease have been the psychiatric effects, including severe anxiety, depression and hallucinations, she said.

“I basically keep putting Band-Aids on all my symptoms,” he said. «A tic turned my life upside down.»

Why is it so difficult to diagnose Lyme?

As the geographic spread of Lyme ticks intensifies, there is an urgent need for more accurate tests that can detect the infection in its early stages, researchers and health officials acknowledge.

“There is no question that Lyme disease and other tick-borne infectious agents are increasing in prevalence,” Strle said.

He The Environmental Protection Agency warns that disease-carrying ticks are more active in warmer temperatures, and climate change will likely mean that the insects will increasingly survive the winter and spread to regions beyond the Northeast, northern California, and mid-northern areas west.

More about Lyme and other tick-borne diseases

Testing for Lyme disease is complicated, especially for doctors unfamiliar with the process, DeBiasi said.

“That leads to a lot of people who have Lyme going undetected or people who have symptoms being told they have Lyme when they really don’t,” he said. «Combine that with bad information on the internet and you end up with a lot of confusion.»

Part of the problem is that once the bacteria is transmitted from a tick to a human, it spreads rapidly through the body at levels that may be too low for a test to detect.

This quickly becomes a detection problem,» explained Brandon Jutras, an associate professor in Virginia Tech’s department of biochemistry.

Serologic tests, which look for antibodies in the blood, are the best method available for diagnosing Lyme disease, experts say. However, antibody tests indicate that the immune system has mounted an attack against a virus or bacteria, but cannot determine whether there is an active infection. They don’t work until the immune system generates a sufficient amount of antibodies, which can take six weeks or more after an initial tick bite.

The CDC recommends using a combination of antibody tests to diagnose Lyme, including an immunoassay antibody test such as ELISA followed by an immunoblot antibody test such as a Western blot test.

Doctors and health officials recognize the need for more reliable tests for Lyme disease that can detect the infection at an early stage.

“We need to do better,” said Jutras, who is working with a Virginia Tech team to develop a rapid Lyme test that can identify the actual infection from the first sign of a tick bite.

“What we really want is a test that says, ‘Does a person still have Borelli spirochete? [Lyme bacteria]and do we need to treat it with antibiotics?’” said Dr. Brian Fallon, director of Columbia University’s Center for Lyme and Tickborne Disease Research.

Controversy over ‘chronic Lyme’

Because testing is inadequate, there is no way to link long-lasting symptoms to initial Lyme infection. Many doctors avoid a diagnosis of chronic Lyme as the term implies a persistent infection.

«There’s no way to say that a Lyme diagnosis from, say, six years ago has anything to do with the symptoms that are occurring now,» DeBiasi said. “Symptoms such as musculoskeletal pain, fatigue, difficulty thinking, and depression are nonspecific. There are many, many possible reasons for those symptoms other than Lyme.»

Fallon of Columbia University prefers the term «long Lyme.»

«‘Chronic’ is a reasonable term if you mean having symptoms on a chronic basis,» Fallon said. “The problem is when someone thinks they have a chronic infection going on and they need more antibiotic treatments.”

DeBiasis insists that the symptoms people experience are real, even if experiences with PTLDS are the exception.

As a pediatric doctor, she has seen panicked parents seek unproven therapies after finding a tick on their child. In a recent study published in the journal pediatric researchDeBiasi and his colleagues found that 75% of children with Lyme disease were better within six months of antibiotics, while 9% had symptoms that affected their functioning after six months.

“If you give them a little bit more time, they seem to make a full recovery,” DeBiasi said.

With the exception of Pfizer and Valneva, which are testing a Lyme disease vaccine in clinical trials, the drug development industry, for the most part, has not focused its energies or dollars on Lyme. Federal research grants are also lacking, Jutras said.

“Many private foundations have stepped up when it comes to research funding for Lyme, but at the federal level, it may be time to revisit some of the priorities when it comes to where we are spending research dollars. ”.

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